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We have developed an easily scalable chromogenic probe for the dual-mode sensing of Spilosoma obliqua Nuclear polyhedrosis viruses (SpobNPV) in aqueous media. The mechanistic investigations establish that the imidazole-mediated hydrolysis of acyl ester linkage in which water (general base) acts as a nucleophile induces a pronounced change in the emission colour from blue to cyan. To the best of our knowledge, this is the first attempt at quantifying OBs of SpobNPV using a small molecule-based optical probe with a detection limit of 2.305 × 10 3 OBs mL -1 . The rate of ester hydrolysis was dependent on both substrate and OBs concentration. Due to the naked eye response, paper strips were also developed for the rapid and onsite detection of SpobNPV. The operation procedure is straightforward and does not involve additional sample preparation steps. This makes the present protocol suitable for daily use. Interestingly, the present protocol is also quite efficient in estimating SpobNPV, even in several agricultural crop samples (for at least 15 crops). Such findings will add a new dimension to better managing Spilosoma obliqua and minimizing the extent of crop loss.

In this report, we describe the methodology for 96 parallel organic syntheses of peptides on Teflon-patterned paper assisted by heating with an infra-red lamp. SPOT synthesis is an important technology for production of peptide arrays on a paper-based support for rapid identification of peptide ligands, epitope mapping, and identification of bio-conjugation reactions. The major drawback of the SPOT synthesis methodology published to-date is suboptimal reaction conversion due to mass transport limitations in the unmixed reaction spot. The technology developed in this report overcomes these problems by changing the environment of the reaction from static to dynamic (flow-through), and further accelerating the reaction by selective heating of the reaction support in contact with activated amino acids. Patterning paper with Teflon allows for droplets of organic solvents to be confined in a zone on the paper array and flow through the paper at a well-defined rate and provide a convenient, power-free setup for flow-through solid-phase synthesis and efficient assembly of peptide arrays. We employed an infra-red (IR) lamp to locally heat the cellulosic support during the flow-through delivery of the reagents to each zone of the paper-based array. We demonstrate that IR-heating in solid phase peptide synthesis shortened the reaction time necessary for amide bond formation down to 3 minutes; in some couplings of alpha amino acids, conversion rates increased up to fifteen folds. The IR-heating improved the assembly of difficult sequences, such as homo-oligomers of all 20 natural amino acids.

A bifunctional fluorescent probe based on a carbazole-pyrimidine conjugate for Hg(2+) and Cu(2+) detection was designed and synthesized. Probe 3 exhibits red shifts in its absorption and fluorescence spectra with significant visual color changes in the presence of these ions. The detection limits of probe 3 for these metal ions were in the nanomolar range. The probe could also be useful as a solid optical sensor for Hg(2+) and Cu(2+).

In this paper, a set of novel ternary deep eutectic solvents (T-DESs) is synthesized and applied in the esterification of 2-methylpropenoic acid with alcohols. T-DESs have multiple functions, serving as a catalyst, polymerization inhibitor, and solvent, and demonstrate excellent catalytic esterification reaction activity (up to 96% yield). The optimal T-DESs 1 can be recycled 14 times without any decrease in its catalytic activity, thus solving the problems of methacrylate product separation with a polymerization inhibitor, catalyst recovery, and organic solvent pollution.

Photochemical transformations of small molecules, such as ortho -substituted benzaldehydes, in the absence of a photocatalyst are significantly underexplored and may reveal unexpected outcomes. In the present paper, we showed that 2-(2-formylphenoxy)acetic acid and its esters undergo photocyclization into chromanone and benzofuranone derivatives under 365 nm irradiation. The reaction occurs exclusively in dimethyl sulfoxide and can be used to efficiently obtain hydroxychromanones in good yields (27-91%). A detailed mechanistic study revealed the clue of the divergent phototransformation with various products.

Substitution of disulfide bonds with a diselenide bonds in peptides and proteins is an often-used strategy to increase the stability of naturally occurring peptides and proteins. In this paper, diselenide metathesis between model diselenide dimer peptides, as well as that in diselenide(s)-substituted biologically active peptides, were analyzed. Surprisingly, depending on the tertiary structure of the peptides, we observed that the metathesis reaction occurs under physiological conditions even in the absence of reducing agents, light and heating.

Due to the high conversion properties, azide compounds are widely utilized in organic synthesis. For instance, azide compounds readily release nitrogen to form a new N-C bond when they function as radical acceptors for the active intermediates in the reaction. Over the past decade, strategies employing azides as radical acceptors to construct nitrogen heterocycles have been extensively developed. This approach has emerged as a crucial method for synthesizing nitrogen heterocycles. Therefore, this paper provides a review of the research advancements in tandem cyclization reactions using azides as radical acceptors, summarizing the process of reaction design, exploration, reasoning of the mechanism, and prospects for further research of these reactions.

In this paper, two near-infrared BODIPY photosensitizers, Id-BDPI and Cz-BDPI, were obtained by modifying the indole and carbazole aromatic heterocycles in the core of BODIPY. The maximum absorption wavelengths of Id-BDPI and Cz-BDPI were 694 nm and 722 nm, and their singlet oxygen yields were 48% and 48.4%, respectively. In the simulated tumor cell photodynamic therapy, Id-BDPI and Cz-BDPI could effectively inhibit the growth of A549 tumor cells under near-infrared light. Meanwhile, the lysosomal co-localization coefficients of Id-BDPI and Cz-BDPI with A549 tumor cells were 0.94 and 0.89, respectively, showing high lysosomal targeting ability and biocompatibility. The two-photon absorption cross sections measured at 1050 nm by the Z -scanning method were 661.8 GM and 715.6 GM, respectively, and Cz-BDPI was further successfully applied to two-photon fluorescence imaging and two-photon excited singlet oxygen generation in zebrafish. The above results indicate that the introduction of aromatic heterocycles can effectively enhance the photodynamic efficacy of BODIPY photosensitizers, and the larger two-photon absorption cross section also brings potential for two-photon photodynamic therapy applications.

In this paper, the hydrogenation of aldehydes and ketones using the RANEY® nickel catalyst was successfully applied for the synthesis of alcohol compounds without additional column chromatographic purification. This synthetic strategy features a wide range of substrates, excellent atom economy, high chemical discrimination and the use of a ligand-free catalytic system. Reactions were performed at room temperature in water providing alcohols in high yields and purity.

Indoles, indolines and hydronaphthylamines are ubiquitous structural motifs in natural products, pharmaceuticals, and biologically active molecules. In this paper, we report the synthesis of aminodihydronaphthyl-substituted indoles and indolines via a Ru-catalyzed carbamoyl-directed C-H functionalization of indoles and indolines with 7-azabenzonorbornadienes. In the presence of Cu(OAc) 2 and AgSbF 6 , [Ru( p -cymene)Cl 2 ] 2 catalyzes the reaction of 1-carbamoylindoles with 7-azabenzonorbornadienes to produce 2-(1-amino-1,2-dihydronaphthalen-2-yl)indoles. Under the same conditions, the reaction of 1-carbamoylindolines with 7-azabenzonorbornadienes affords 7-(1-amino-1,2-dihydronaphthalen-2-yl)indolines. In both cases, the reactions yield cis -configured products.

The synthesis of polyketide natural products has been a captivating pursuit in organic chemistry, with a particular focus on selectively introducing 1,3-polyol units. Among these natural products, Marinomycins A-D have garnered substantial interest due to their exceptional structural features and potent cytotoxicity. In this paper, we present a novel approach for synthesising the monomeric counterparts of Marinomycin A and B. Our method employs a previously established iterative cycle in conjunction with a standardised polyketide building block. Through this strategy, we showcase a promising pathway towards total and partial syntheses of these intriguing natural products.

The development of luminescent molecular materials has advanced rapidly in recent decades, primarily driven by the synthesis of novel emissive compounds and a deeper understanding of excited-state mechanisms. Herein, we report a streamlined synthetic approach to light-emitting diazapolyoxa- and polyazamacrocycles N 2 C n O x Q and N y C n Q ( n = 3-10; x = 2, 3; y = 2-5), incorporating a 2,3-diphenylquinoxaline residue (DPQ). This synthetic strategy based on macrocyclization through Pd-catalyzed amination reaction yields the target macrocycles in good or high yields (46-92%), enabling precise control over their structural parameters. A key role of the PhPF- t Bu ligand belonging to the JosiPhos series in this macrocyclization was elucidated through DFT computation. This macrocyclization reaction eliminates the need for complex protecting-deprotecting procedures of secondary amine groups, offering a convenient and scalable method for the preparation of target compounds. Moreover, it boasts a potentially broad substrate scope, making it promising for structure-properties studies within photophysics, sensor development, and material synthesis. Photophysical properties of representative macrocycles were investigated, employing spectroscopic techniques and DFT computation. It was demonstrated that DPQ-containing macrocycles display aggregation-induced emission in a DCM-hexane solvent mixture despite the presence of flexible tethers within their structures. Single-crystal X-ray diffraction analysis of a representative compound N 2 C 8 O 3 Q allowed us to gain deeper insight into its molecular structure and AIE behaviour. The emissive aggregates of the N 2 C 10 O 3 Q macrocycle were immobilized on filter paper yielding AIE-exhibiting test strips for measuring acidity in vapors and in aqueous media.

Bromonitroalkenes are useful molecules in synthetic organic chemistry. They are mainly prepared from nitroalkenes via bromination reactions. In this review, the application of bromonitroalkenes as partners in the reaction with a diversity of mono- and bi-functional molecules, including aldehydes and ketones, active methylene compounds, 1,2-dicarbonyls, enamines, enols, electron-rich arenes, amidines, azomethine ylides, azirines, diazo compounds, and many others, is reviewed. By using these substrates, various biologically active scaffolds, such as heterocycles, carbocycles, spirocycles, polycyclic systems, natural products, and other useful acyclic compounds, were prepared. In addition, due to their dielectrophilic character, electrophilic and nucleophilic character, and ability to participate in cycloaddition reactions, bromonitroalkenes were efficiently applied in asymmetric cascade/domino/tandem reactions catalyzed by chiral catalysts. In this manuscript, around 55 papers are summarized and discussed during the years 2000-2023.

Berberine (BBR), a widely used isoquinoline alkaloid derived from natural sources, exhibits aggregation-induced emission (AIE) characteristics and has biological applications such as in selective lipid droplet imaging and photodynamic therapy. However, natural BBR suffers from low fluorescence quantum yield ( Φ ) and monotonous emission wavelength. In this paper, a series of C9-position-aryl-substituted berberine derivatives with a D-A structure were designed and synthesized. The electronic effect of the substitution groups can tune the intramolecular charge transfer (ICT) effect of the berberine derivatives, resulting in bluish green to NIR (508-682 nm) luminescence with AIE characteristics and enhanced F ) and monotonous emission wavelength. In this paper, a series of C9-position-aryl-substituted berberine derivatives with a D-A structure were designed and synthesized. The electronic effect of the substitution groups can tune the intramolecular charge transfer (ICT) effect of the berberine derivatives, resulting in bluish green to NIR (508-682 nm) luminescence with AIE characteristics and enhanced Φ F up to 36% in the solid state. Interestingly, berberine derivatives containing an amino or a pyridyl group can exhibit fluorescence response to TFA. Cell imaging of the berberine derivatives was conducted using Caco-2 cancer cells, demonstrating their multi-color and efficient wash-free imaging capabilities. This work presents a new strategy for developing novel berberine derivatives with tunable AIE properties for application in biological imaging.

The first example of the synthesis of 4-oxobutane-1,1,2,2-tetracarbonitriles (OTCs) containing a phenolic moiety has been described. The synthesis is based on the reaction between tetracyanoethylene and 4-hydroxyphenyl-substituted ketones under mild conditions. Due to the presence of a phenolic hydroxyl group, these compounds are more functionalized derivatives of the well-known OTC substrates used for diversity-oriented synthesis (DOS). The preserved synthetic potential of the OTCs for the preparation of phenol-containing derivatives with enhanced capabilities for tuning optical properties has been shown using the targeted synthesis of 2-(2-oxo-1,2-dihydro-3 H -pyrrol-3-ylidene)malononitriles. Based on the obtained pyrroles and a model amine (pyrrolidine) a previously unknown type of thermosensitive three-position molecular switch is described. Reversible color changes of the dye are shown in both solution and on filter paper. The results reveal a new research branch of the OTC-based DOS strategy to access functionalized phenol-containing derivatives.

Cytochalasans are fungal metabolites that are known to inhibit actin polymerization. Despite their remarkable bioactivity, there are few studies on the structure-activity relationship (SAR) of the cytochalasan scaffold. The full potential of structural modifications remains largely unexplored. The substituent at position 10 of the cytochalasan scaffold is derived from an amino acid incorporated into the cytochalasan core, thus limiting the structural variability at this position in natural products. Additionally, modifications at this position have only been achieved through semisynthetic or mutasynthetic approaches using modified amino acids. This paper introduces a modular approach for late-stage modifications at position 10 of the cytochalasan scaffold. Iron-mediated cross-coupling reactions with corresponding Grignard reagents were used to introduce aryl or benzyl groups in position 10, resulting in the synthesis of six new cytochalasan analogues bearing non-natural aromatic residues. This methodology enables further exploration of modifications at this position and SAR studies among cytochalasan analogues.

This report covers boron tribromide (BBr 3 ) mediated dearomative spirocyclization of biaryl ynones. The direct synthesis of spiro[5.5]dienones with a tri-substituted double bond is described for the first time in this paper. The scope of the reaction is broad and the spirocyclic products were obtained in moderate to good yields.

2,5-Disubstituted furans are frequently found in pharmaceuticals and bioactive natural products. Nucleophilic substitution reactions on the carbon atom adjacent to the furan ring are useful for producing various furan derivatives. However, the formation of 5-substituted 2-halomethylfuran and the subsequent nucleophilic substitution reactions are often limited by severe undesired reactions caused by the highly reactive halomethylfurans. This paper reports the successful rapid synthesis of various 2,5-disubstituted furans using microflow technology, which suppresses undesired reactions including dimerization and ring opening of the furans. We observed that Brønsted acids had a significant effect on the nucleophilic substitution reaction and the use of HBr and HI gave the best results. A plausible mechanism of the Brønsted acid-mediated nucleophilic substitutions in the developed approach was proposed.

Considerable research attention has been devoted to the development of portable and rapid fluorescence sensors that can selectively detect volatile acids, due to the harmful effects of acid vapour on the environment and human health. Although various types of fluorophores have been reported for sensing volatile acid vapours, regulation of the sensory response using aggregation induced emissive (AIE) based gelators has rarely been reported. In this study, we present the design and synthesis of a novel organogelator that is capable of sensing volatile acids through AIE. An acridine-attached poly(aryl ether) dendron molecular system is synthesized through an aldimine coupling reaction, which self-assembles and forms a gel, exhibiting AIE behavior. The synthesized molecule and prepared gel were characterized using NMR, MASS, XRD, HRSEM and rheology techniques. The AIE property of APD was investigated using steady-state absorption and emission spectroscopic techniques. The sensory response of the APD gelator was tested with various analytes, and the results indicated that APD shows rapid response, particularly to acid vapours, where the detection limits (DL) of trifluoroacetic acid (TFA), hydrochloric acid (HCl) and nitric acid (HNO 3 ) vapor were as low as 0.22, 0.9 and 0.30 ppm, respectively. An APD solid film in filter paper shows a visual color change from yellow to red in an aqueous acidic medium, and the effect is reversed in an alkaline medium. These findings suggest that an APD gelator could potentially be utilized to generate a portable acid vapor sensor kit due to its low detection limit and rapid response time, and it could be also be used as a substitute for existing acid indicators.

In this paper, three fluorescent protein chromophore analogs PFPAr (PFPP, PFPC, and PFPT) were synthesized and proved to be useful for photodynamic therapy and two-photon fluorescence imaging. By adding five- or six-membered aromatic heterocycles to the photosensitizer PFP, we obtained three fluorescent protein photosensitizers PFPAr with better performances. As a demonstration, compared with the reported photosensitizer PFP, photosensitizer PFPP exhibits larger emission wavelengths (701 nm) and achieves a slight enhancement in the efficiency of singlet oxygen ( Φ Δ = 23%). Notably, PFPP can perform good two-photon fluorescence imaging with an 800 nm femtosecond laser in zebrafish. In in vitro cytotoxicity assays, PFPP shows good phototoxicity (IC 50 = 4.12 μM) and acceptable dark toxicity (cell viability assay >90%). The reactive oxygen imaging experiments and AO/EB double staining assay indicate that PFPP can generate singlet oxygen to eliminate A-549 tumor cells effectively with photoexcitation of 460 nm blue light (20 mW cm -2 ). Furthermore, PFPP can label the lysosomes of tumor cells with high specificity for lysosomes (Pearson's correlation coefficient of 0.91). Thus, our study demonstrated that the rational introduction of aromatic heterocycles into fluorescent protein photosensitizers can effectively enhance the key parameters of photosensitivity and pave the way for further two-photon photodynamic therapy.

This paper describes the development and performance of catalytic DNA-based nanocranes for the controlled modification of wild-type proteins. We show that the position of the catalyst offers control over the region of modification, and that reversible interactions between the catalytic structure and thrombin enable trigger-responsive modification, even in cell lysate.

A new fluorescent probe SWJT-23 with lysosomal targeting ability for detection of hypobromous acid (HBrO) was synthesised based on the naphthalimide skeleton. This probe exhibited a fast response (within 3s), a low detection limit (1.24 nM), excellent selectivity and a high fluorescence quantum yield ( Φ = 0.490). Moreover, SWJT-23 not only realized the sensitive detection of HBrO in cells and water samples, but also was fabricated as a paper-based sensor. In consequence, SWJT-23 is expected to be an efficient and powerful tool for monitoring HBrO in organisms and the environment in realistic scenarios.

Aryl radicals are intermediates in many reactions, but determining their presence unambiguously is often challenging. As we recently reported, reaction of 2-iodo-1,3-dimethylbenzene (7) in benzene with KO t Bu and a suitable organic additive, leads to a base-induced homolytic aromatic substitution (BHAS) coupling reaction giving 2,6-dimethylbiphenyl (12) and biphenyl (3) as coupled products, together with xylene (13). In this case, biphenyl arises from a radical translocation and is the major coupling product. This paper now quantitatively investigates that reaction, which shows a very similar ratio for 3 : 12 [ ca. 4 : 1] when using different sources of radical initiation. Deuterium isotope studies provide detailed mechanistic support for the proposed mechanism; when carried out in C 6 D 6 vs . C 6 H 6 , the reaction is characterised by a strong isotope effect for formation of 3- d 10 vs . 3, but not for formation of 12- d 5 vs . 12. These distinctive properties mean that the transformation can act as an assay for aryl radicals. An advantage of such a BHAS process is its sensitivity, since it involves a chain reaction that can amplify radical activity.

This paper describes a simple and practical protocol for the direct synthesis of acyclic and cyclic quinone derivatives via an acid-promoted nickel(II)-catalyzed inner rim C-H oxidation of cyclotriveratrylene (CTV) and its analogues. The cyclic quinone derivatives resulted from trimethoxy-cyclotriveratrylene (TCTV) through C-C bond formation via intramolecular ipso substitution followed by subsequent anionic rearrangement containing stereo-vicinal quaternary centers. The DFT calculations strongly support the experimental findings and reveal the role of Brønsted acids in the C-H bond activation of CTV. All the newly synthesized compounds were screened for their in vitro anti-cancer activity using colorimetric SRB assay analysis. Among them, compounds 3a, 3d, 3h, 4a, 4b, 4c and 4e exhibited moderate anticancer activity against A549, HCT-116, PC-3, MDA-MB-231, HEK-293 and SW620 human cancer cell lines.

This paper reports a novel method for the visible-light-mediated synthesis of quinazolinones from the reaction of benzyl bromides with 2-aminobenzamides. The reaction proceeded efficiently at room temperature upon irradiation with an 18 W blue light-emitting diode in air without photocatalysts or additives. By varying the solvent type, substrate molar ratio, and reaction time, the optimal reaction conditions, including the use of methanol solvent, room temperature, and reaction time of 28 h, were identified. Under these conditions, various quinazolinones were obtained using 18 substrates, with the highest yield of 93%. To determine the industrial value of the proposed method, a scale-up reaction was performed and 80% product yield was achieved. Mechanistic studies revealed that the reaction likely proceeded via a radical pathway and that the hydrogen bromide by-product generated during the first step of the reaction of benzyl bromide with 2-aminobenzamide promoted the subsequent step.

Biphenyl-fused-dioxacyclodecynes are a promising class of strained alkyne for use in Cu-free 'click' reactions. In this paper, a series of functionalised derivatives of this class of reagent, containing fluorescent groups, are described. Studies aimed at understanding and increasing the reactivity of the alkynes are also presented, together with an investigation of the bioconjugation of the reagents with an azide-labelled protein.

Murepavadin (POL7080) in phase III clinical trials, a backbone-cyclized polypeptide composed of 14 amino acids, has a novel mode of action and shows a specific and efficient bactericidal effect against multidrug-resistant Pseudomonas aeruginosa . It is a potential candidate to treat severe P. aeruginosa infections in the future and still has significant commercial value for further research and development. In this paper, we report a liquid-phase peptide synthetic route for this valuable candidate polypeptide assisted by hydrophobic-support materials (tags), which overcomes the difficulties of high cost and poor yield in the traditional solid-phase synthesis of macrocyclic peptides. Through the careful optimization of reaction conditions and the innovative strategy of synthetic post-treatment, we established a simple and efficient liquid-phase synthetic route suitable for POL7080 and other similar structures, with satisfactory yield, high purity and a production process not being controlled by scale.

An efficient and convenient method for the synthesis of 2-trifluoromethyl benzimidazoles is described in this paper. The cyclization reaction of various o -phenylenediamines with hexafluoroacetylacetone proceeded smoothly in the presence of Cu 2 O as the catalyst to produce 2-trifluoromethyl benzimidazoles in satisfactory to excellent yields (up to >99% yield). The CF 3 source, hexafluoroacetylacetone, acted not only as cyclization partner, but also acted as a ligand for the Cu catalyst. Various synthetically useful functional groups, such as halogen atoms, cyano, and methoxycarbonyl groups, remained intact during the cyclization reactions. The reaction mechanism was thoroughly investigated and was determined to involve a seven-membered cyclic diimine intermediate.

In this study, we report a fluoride chemosensor based on the use of a non-fluorescent pre-coumarin, compound 1. This compound undergoes selective fluoride-triggered formation of coumarin 2, with a concomitant turn-on fluorescence signal. Although compound 1 exists as a mixture of alkene isomers (2 : 1 in favor of the E isomer), only the minor Z -isomer undergoes cyclization. Nonetheless, comprehensive computational and experimental studies provide evidence that in situ isomerization of E -1 to Z -1, followed by fluoride-triggered phenolate evolution and intramolecular cyclization, facilitates the generation of coumarin 2 in high yield. Moreover, this system is an effective turn-on fluorescence sensor for fluoride anions, which displays outstanding selectivity (limited response to other commonly occurring analytes), sensitivity (lowest reported limits of detection for this sensor class), and practicality (works in solution and on paper to generate both fluorometric and colorimetric responses). Ongoing efforts are focused on expanding this paradigm to other pre-coumarin scaffolds, which also undergo analyte-specific coumarin formation accompanied by turn-on fluorescence.

The interest of scientists in the carbazole core has risen steadily over the last 30 years, particularly over the last decade given its presence in several active pharmaceutical ingredients, functional materials and a wide range of biologically active natural products. The continuous development of more efficient, more (regio-)selective and "greener" methodologies to access the carbazole core is thus imperative. This review compares and evaluates synthetic strategies towards the carbazole core that have been reported since 2013, with a focus on their applicability towards the total synthesis of carbazole-containing natural products.

The paper details an electrochemical method that couples olefins with benzotriazoles to form C(sp 2 )-N bonds, enabling the synthesis of N -vinyl benzotriazoles in moderate to good yields. n Bu 4 NI functions as both an electrolyte and an iodine mediator, and the method does not require oxidants or metals. It is a highly atom-economical and clean reaction, with hydrogen as the sole byproduct.

In this paper, the vinyl-pyridine group was used to modify the BODIPY dimer photosensitizer (T-BDP2) to obtain a VP-BDP2 photosensitizer. Compared with the T-BDP2 photosensitizer, the VP-BDP2 photosensitizer could work under pure water conditions, the singlet oxygen yield was increased from 9.38% to 22.2%, the charge transfer rate was increased from about 30 ps to about 10 ps, and the red emission was enhanced in fluorescence imaging. In addition, the VP-BDP2 photosensitizer could also generate the superoxide radical (O 2 ˙ - ) under pure water conditions. The ROS generation mechanism of the VP-BDP2 photosensitizer was considered to be the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism, which was verified by fs-transient absorption spectra and theoretical calculation. In the photodynamic therapy of A-549 cells, the VP-BDP2 photosensitizers could generate singlet oxygen and superoxide radicals (O 2 ˙ - ) under biological conditions, and showed high phototoxicity with the IC 50 value at 12.1 μM under light at 525 nm. Additionally, the multiple dipolar configuration meant that the VP-BDP2 photosensitizer could be used in two-photon fluorescence zebrafish imaging under 800 nm excitation, which sets the stage for future two-photon photodynamic therapy.

By a hydroamination-induced tandem annulation process, we herein report a new three-component reaction for room temperature construction of carbo-bridged polyheterocycles with exclusive diastereoselectivity, which features readily available feedstocks, catalyst-free conditions, good substrate and functionality compatibility, no need for transition metal catalysts, and high step and atom efficiency. The products are formed via initial formation of 1,2-dihydro-3 H -pyrazol-3-one nucleophiles from but-2-ynedioates and hydrazine followed by 2,4-difunctionalization of N -heteroarenium salts. Given that the obtained products possess structurally important tetrahydroquinoline and pyranopyrazole motifs, the developed chemistry is anticipated to be further applied to the discovery of functional molecules including biomedical ones.

Fe(II)/2OG-dependent oxygenase γ-butyrobetaine hydroxylase (BBOX) stereoselectively hydroxylates inactive C-H bonds and produces L-carnitine. It has potential applications in the biosynthesis of L-carnitine and the synthesis of other small molecule alcohols. In this paper, we systematically explore the substrate range of Pseudomonas sp. AK1 BBOX (psBBOX), with emphasis on the quaternary ammonium portion of γ-butyrobetaine (γ-BB). The space limitation of the "aromatic cage" in psBBOX in the hydroxylation of large quaternary ammonium analogues was studied, and the role of four aromatic amino acid residues in the substrate binding mode was analyzed. Consequently, the F188A mutant was developed with the ability to hydroxylate cyclic quaternary ammonium analogues and generate new alcohol compounds by breaking the limitation of the "aromatic cage".

This paper describes the base-mediated cascade reactions of 4-chloro-3-substituted coumarins with α-aminomaleimides, allowing the efficient synthesis of dihydrochromeno[4,3- d ]pyrrolo[3,4- b ]pyridines with interesting chemoselectivity. These transformations include the domino-style formation of C-C/C-N bonds through a base-mediated nucleophilic substitution, Michael addition, N -cyclization, and elimination. The presented synthetic strategy has several advantages: it is simple, uses readily available starting materials and an environmentally friendly solvent, has a highly chemoselective route, and allows the purification of products via washing with EtOH (96%), a technique called GAP (Group-Assisted-Purification) chemistry.

An acetoxy naphthaldehyde conjugated benzophenoxazinium chloride chromophore-based-donor-π-acceptor (D-π-A) fluorescent probe BPN (benzophenoxazinium naphthoxy imine) displaying near-infrared (NIR) emission was reported for hydrazine detection. The chosen water-soluble benzophenoxazinium chloride chromophore has excellent photostability, a high molar extinction coefficient and fluorescence quantum yield ( Φ = from 0.0075 to 0.6193), higher selectivity towards hydrazine and a longer fluorescence lifetime. In the presence of hydrazine, BPN exhibits near infrared fluorescence emission at 725 nm along with color change from light blue to red, as detected by the naked eye. Moreover, the BPN probe can selectively detect hydrazine (DL = 4.5 × 10 -10 M) in a 90% aqueous DMSO solution without interfering with other analytes. As proof of real samples, the probe is successfully applied to sense hydrazine in thin layer chromatography (TLC) paper strips (both solution and vapor phases) and water and soil samples, suggesting its significant potential application. Also, due to its NIR emission and aqueous solubility, the BPN probe can be successfully used in live cell imaging with low cytotoxicity.

Chemists learn the most important transformations of the carboxylic acid functionality (COOH) from as early as the first semester of their studies. Carboxylic acids are not only safe to store and handle, but also broadly accessible with great structural diversity either from commercial sources or by means of a large variety of well-known synthesis routes. Consequently, carboxylic acids have long been recognized as a highly adaptable starting material in organic synthesis. A large body of reactions of carboxylic acids are based on catalytic decarboxylative conversions, in which the COOH group of carboxylic acids is catalytically replaced without trace by extrusion of CO 2 chemo- and regioselectively. Within the last two decades, the area of catalytic decarboxylative transformations has expanded significantly by utilizing various classes of carboxylic acids as the substrate, including (hetero)aromatic acids, alkyl acids, α-keto acids, α,β-unsaturated acids and alkynoic acids. A literature survey reveals that compared to aromatic acids, the number of original research papers on decarboxylative reactions of α-keto acids, α,β-unsaturated acids and alkynoic acids has been rising every year lately, particularly within past five to six years. The prime aim of the current review is to give an overview of the decarboxylative transformations of α-keto acids, α,β-unsaturated acids and alkynoic acids that have been developed since 2017. The article focuses on the decarboxylative functionalizations that occur in the presence or absence of transition metal catalysts and/or under photoredox catalysis.

In this paper, we describe the synthesis and properties of a Golgi-targeting fluorescent probe for the selective detection of chloride anions. Specifically, we have synthesized one quaternized quinoline derivative bearing a sulfanilamido group and found that this compound is able to primarily target the Golgi apparatus and detect the changes in the concentration of cellular chloride anions.

This paper describes the iron-catalyzed photochemical carbonylation of benzylic C-H bonds resulting in the synthesis of various aryl ketones. Using 5 W blue LED irradiation, the reactions proceed smoothly in the presence of 2 mol% of FeBr 3 in MeOH at 35 °C. The catalytic system could be extended for the oxidation of silane, thioether, and phosphine into silenol, sulphoxide, and phosphoxide, respectively. A mechanistic study suggests that a hydrogen bond-stabilized iron-hydroperoxo species is the reactive intermediate. It is shown that the reaction proceeds via a four-electron-transfer pathway, and a benzylic cation seems to be the crucial reactive species. The method is applied for the synthesis of pomalyst, haloperidol, melperone, and lenperone.

Phase separation is a common biological phenomenon in the liquid environment of organisms. Phase separation has been shown to be a key cause of many existing incurable diseases, such as the protein aggregates formed by phase separation of Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, etc . Tracking the occurrence of phase separation in vivo is critical to many disease detection methods and solving many treatment problems. Its physicochemical properties and visual detection methods have flourished in the last few years in chemical biology, among which the fluorogenic toolbox has great application potential compared to the traditional detection methods that cannot visualize the phase separation process intuitively, but just show some parameters indirectly. This paper reviews the mechanism and disease correlation proven in recent years for phase separation and analyzes the detection methods for phase separation, including functional microscope imaging techniques, turbidity monitoring, macromolecule congestion sensing, in silico analysis, etc . It is worth mentioning that the qualitative and quantitative analysis of aggregates formed by phase separation using in vitro parameters has successfully provided basic physical and chemical properties for phase separation aggregates, and is an important cornerstone for researchers to carry forward the past and break through the existing technical shackles to create new in vivo monitoring methods such as fluorescence methodology. Crucially, fluorescence methods for cell microenvironment imaging based on different mechanisms are discussed, such as AIE-based probes, TICT-based probes and FRET-based probes, etc .

Amongst the various existing methods of analyte quantification, fluorescent-based methods, especially the ratiometric methods, continue to gain significant attention due to their high reproducibility, low environmental influence, and self-calibrating behavior. This paper presents the modulation in a monomer-aggregate equilibrium of coumarin-7 (C7) dye at pH ∼ 3, under the influence of a multi-anionic polymer, poly(styrene sulfonate) (PSS), leading to a significant modification in the ratiometric optical signal of the dye. At pH ∼ 3, cationic C7 formed aggregates in the presence of PSS via a strong electrostatic interaction, resulting in the development of a new emission peak at 650 nm at the expense of the monomer emission at 513 nm. Such contradicting changes in fluorescence intensities at two different wavelengths gave rise to a ratiometric signal, which was found to be highly sensitive towards external stimuli such as pH, and ionic strength. The stability of the C7-PSS complex was found to decrease as the pH of the solution was increased beyond 5, which indicated the decline in the electrostatic attraction between C7 and PSS due to the deprotonation of the C7 dye. Furthermore, an increase in the monomeric peak and a concomitant decrease of the aggregate peak with added salt in the solution (at pH ∼ 3) clearly justified the presence of an electrostatic attraction between C7 and PSS for the complex formation. This was further validated by the excited-state lifetime measurement of the C7-PSS complex, which showed a systematic increase in lifetime contribution from the monomeric species at the expense of aggregated species, as the concentration of NaCl increased in the solution. Thus, protamine (Pr), being a highly positively charged polypeptide, largely affected the monomer-aggregate equilibrium of the C7-PSS system, leading to a phenomenal change in the ratiometric signal, which was utilized to quantify with LOD as low as ∼2.8 nM in buffer for the bio-analyte Pr. Moreover, the ratiometric response of the C7-PSS assembly demonstrated excellent selectivity towards Pr, facilitating its practical relevance for the quantification of Pr in a 1% human serum matrix. Therefore, the studied C7-PSS can be utilized as a potential candidate for the quantification of the protamine even in complex biological media.

Terpenes and their derivatives are natural antifungal and antimicrobial agents. In this paper, potential antifungal agents were developed on the basis of farnesol, geraniol, myrtenol, perillyl alcohol, cedrol and phytol. The synthesized compounds exist in aqueous solutions as stable associates ( D = 142-216 nm, PDI 0.04-0.16, Z = +0.9-+46 mV). Formation of stable associates of the compounds in solution promotes compaction and dosed release of the drug. The membranotropic activity of the compounds was also investigated to open up their possible application in the treatment of skin diseases. The relationship between membranotropism and lipophilicity coefficient (log  P ) has been established. The antifungal and antimicrobial activities of the obtained compounds were studied in vitro on the clinical isolate of Candida sp., Candida albicans , yeast Saccharomyces cerevisiae , Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus , Bifidobacterium bifidum ) bacteria. Candida sp. (0.0781 mg mL -1 ) and Saccharomyces cerevisiae (0.0049 mg mL -1 ) showed the highest sensitivity to the agents.

Protocellular surface formation via the self-assembly of amphiphiles, and catalysis by simple peptides/proto-RNA are two important pillars in the evolution of protocells. To hunt for prebiotic self-assembly-supported catalytic reactions, we thought that amino-acid-based amphiphiles might play an important role. In this paper, we investigate the formation of histidine-based and serine-based amphiphiles under mild prebiotic conditions from amino acid : fatty alcohol and amino acid : fatty acid mixtures. The histidine-based amphiphiles were able to catalyze hydrolytic reactions at the self-assembled surface (with a rate increase of ∼1000-fold), and the catalytic ability can be tuned by linkage of the fatty carbon part to histidine ( N -acylated vs . O -acylated). Moreover, the presence of cationic serine-based amphiphiles on the surface enhances the catalytic efficiency by another ∼2-fold, whereas the presence of anionic aspartic acid-based amphiphiles reduces the catalytic activity. Ester partitioning into the surface, reactivity, and the accumulation of liberated fatty acid explain the substrate selectivity of the catalytic surface, where the hexyl esters were found to be more hydrolytic than other fatty acyl esters. Di-methylation of the -NH 2 of OLH increases the catalytic efficacy by a further ∼2-fold, whereas trimethylation reduces the catalytic ability. The self-assembly, charge-charge repulsion, and the H-bonding to the ester carbonyl are likely to be responsible for the superior (∼2500-fold higher rate than the pre-micellar OLH) catalytic efficiency of O -lauryl dimethyl histidine (OLDMH). Thus, prebiotic amino-acid-based surfaces served as an efficient catalyst that exhibits regulation of catalytic function, substrate selectivity, and further adaptability to perform bio-catalysis.

Polyamines are ubiquitously found in nature. In this paper, we disclose our iterative coupling strategy for the synthesis of a structurally defined polymer of 1,3-propanediamine, and the polymer can be used for the synthesis of both the initially proposed structure and the revised structure of protoaculeine B isolated from a marine sponge. We first attempted the synthesis of polyamines using "the Ns strategy" but found that a polyamine with eleven Ns groups has solubility problems. We then examined the versatility of the photoremovable NPEC protecting group in polyamine synthesis. Finally, the synthesis of a suitably protected 12-mer polyamine was achieved employing the NPEC group for the temporary protection of a terminal amino group.

The reactions of direct Csp 2 -H chalcogenylation and halogenation of N -arylpyrrolidone under the action of PIFA without a directing group and under metal-free conditions were reported in this paper. Diphenyl selenide/sulfur and selenium phenyl halides were used as reaction reagents to obtain chalcogenylated and halogenated N -arylpyrrolidone products, respectively. The mechanistic studies indicated that a radical pathway was likely involved in these reactions. Preliminary antitumor tests showed that these compounds have moderate to potent activities against human acute leukemia cells K562 in vitro , which may be used as lead compounds for subsequent research.

The green fluorescent protein (GFP) is a purely natural specialty protein that has been widely used to design synthetic fluorescent probes. In the present work we designed and synthesized a series of fluorescent compounds akin to GFP precursors by a one-step method, and investigated the luminescence properties of the fluorescent compounds by varying the substituents. We presented the first systematic summary of the photophysical data including extinction coefficients and fluorescence quantum yields for this class of fluorescent dyes. We also carried out density functional theory (DFT) calculations for these dyes to investigate the effect of electronic effects due to different substituents. These studied optical properties may provide a reference for later probe design. More interestingly, we have developed a polarity-sensitive lipid droplet probe T-LD with AIE properties on this basis. The probe exhibited not only favorable pH stability and kinetic stability in terms of optical properties, but also solvent discolouration and polarity-sensitive properties, and was able to label intracellular lipid droplets. We successfully applied the probe for intracellular lipid droplet level monitoring and zebrafish imaging.

The applications of 2-hydroxy-β-nitrostyrenes as efficient bifunctional intermediates in organic synthesis are investigated in this review. For this purpose, reactions of 2-hydroxy-β-nitrostyrenes with diverse molecules, including carbonyl compounds, 1,3-dicarbonyl compounds, α,β-unsaturated carbonyl compounds, hemiacetals, nitroalkenes, γ-butenolides, tetronic acid, azalactones, pyrazolones, enamines, malononitrile, methyleneindolinones, ylides, etc. , were investigated to construct interesting biologically active scaffolds such as chromans, chromenes, coumarins, benzofurans and their fused and spiro rings, natural products, and other useful cyclic and acyclic compounds. The main focus is on the asymmetric synthesis of these compounds via cascade/domino/tandem reactions catalyzed by chiral organocatalysts. In this review, around 60 papers reported between the years 2000 and 2022 are presented.

We report a Pd(II)-catalyzed bidentate directing group 8-aminoquinoline-aided, site-selective β-C-H functionalization protocol for assembling modified azobenzene carboxamides. Considering the importance of azobenzenes in chemical sciences, this paper reports a new route for enriching the library of modified azobenzene motifs.

A novel approach for the production of halogen cations through the reaction of halogens with silver ions is described in this paper. On this basis, the regioselective synthesis of 3-haloquinolines and 3-halospirocyclohexadienones is realized through solvent regulation. The gram-scale reaction and the compatibility of complex substrates demonstrate the synthetic potential of this protocol, which will be an appealing strategy in organic synthesis.

In this paper, we report a synthetic protocol for the construction of biaryl motif-based or π-extended azobenzene and alkylated azobenzene derivatives via the Pd(II)-catalyzed bidentate directing group (DG)-aided C-H activation and functionalization strategy. In the past, the synthesis of biaryl motif-based azobenzenes was accomplished through the traditional cross-coupling reaction involving organometallic reagents and aryl halides or equivalent coupling partners. We have shown the direct coupling of C-H bonds of aromatic/aliphatic carboxamides (possessing a DG) with iodoazobenzenes as the coupling partners through the Pd(II)-catalyzed bidentate DG-aided, site-selective C-H functionalization method. Azobenzene-containing compounds are a versatile class of photo-responsive molecules that have found applications across branches of chemical, biological and materials sciences and are prevalent in medicinally relevant molecules. Accordingly, the synthesis of new and functionalized azobenzene-based scaffolds has been an attractive topic of research. Although the classical methods are efficient, they need pre-functionalized starting materials. This protocol involving the Pd(II)-catalyzed, directing group-aided site-selective C-H arylation of aromatic and aliphatic carboxamides using iodoazobenzene as the coupling partner affording azobenzene-based carboxamides is an additional route and also a contribution towards enriching the library of modified azobenzenes. We have also shown the photoswitching properties of representative compounds synthesized via the Pd(II)-catalyzed directing group-aided site-selective C-H functionalization method.